The objective of the proposed work is to study the mechanism of gelation of deoxyhemoglobin and to find means of preventing deoxyhemoglobin S (deoxyHb S) polymerization. Our working hypothesis is that oligopeptides mimicking portions of the amino acid sequence of Hb S at the intermolecular contact sites can interfere with aggregation of the molecules but without resort to chemical modifications of the protein. The mutation site (beta S6 region) is generally believed to be one of the contact sites. This is supported by the finding that the hexapeptide beta S1-6 can raise the minimum gelling concentration (MGC) by about 90 percent at molar ratios (peptide/heme) of 2 to 3. Likewise, the octapeptide beta 77-84 is equally effective as beta S1-6, suggesting that the region between helices E and F of the beta chain of Hb S might be another contact site. Certain amino acids such as L-homoserine have been reported to inhibit the sickling of sickle cells. However, we find that these compounds do not affect the MGC of deoxyHb S, nor increase the filterability of the erythrocytes.